Status of HRD That Lead to a Benefit From Olaparib in Combination With Bevacizumab (STROBE Trial)

NCT06377267 | Recruiting Phase 2

• 1 other identifier: ESR-20-21103
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The study aims to address the challenge of accurately identifying patients with ovarian cancer who would benefit from poly-ADP ribose inhibitors (PARPi) as first-line maintenance therapy. While BRCA1/2-mutated epithelial ovarian cancer (EOC) patients have shown significant benefits from PARPi treatment, the efficacy in homologous recombination deficient (HRD) patients remains inconclusive. Current assays used to estimate HR status do not effectively differentiate between patients who benefit most from PARPi and those who do not, making it inefficient to treat all patients. There is a need for a more accurate HR status testing method to optimize PARPi benefit. This study aims to assess the performance of the VHIO-CARD-300 test in determining HR status compared to SOPHiA DDM™ Dx HRD Solution. Summary: The study is a prospective, non-randomized trial designed to evaluate the concordance of the VHIO-CARD-300 test in establishing HR status compared to SOPHiA DDM™ Dx HRD Solution. Additionally, it aims to assess the association between HRD status determined by the VHIO-CARD-300 test and treatment efficacy. Patients with advanced FIGO stage III-IV high grade serous or endometrioid ovarian, fallopian tube, or peritoneal cancer will be invited to participate. Those eligible will undergo testing with both VHIO-CARD-300 and SOPHiA DDM™ Dx HRD Solution. Patients classified as HRD positive will receive olaparib in combination with bevacizumab, while others will receive bevacizumab alone. Treatment will be administered according to approved doses, with follow-up evaluations conducted until RECIST progression.

Conditions

Ovarian Cancer

Keywords

HRD status

Outcome Measures

Primary Outcomes (1)

• Concordance in HRD status identification between VHIO-CARD-300 test and SOPHiA DDM™ Dx HRD Solution

  The primary outcome measure description would outline the method used to evaluate the agreement in HRD status identification between the VHIO-CARD-300 test and SOPHiA DDM™ Dx HRD Solution. This would include details on how HRD status is determined and compared between the two tests, along with any statistical analyses employed to measure the level of agreement.

  Through study completion, an average of 1.5 years

Secondary Outcomes (5)

• Performance Assessment of VHIO-CARD-300 Test for HR Status Identification

  Through study completion, an average of 1.5 years

• Association Between VHIO-CARD-300 Test Groups and Efficacy Outcomes(i.e., HRD positive and HRD negative) and efficacy outcomes.

  Through study completion, an average of 1.5 years

• Analysis of Progression-Free Survival (PFS) and Overall Survival (OS) in Discrepant HRD Cases

  Through study completion, an average of 1.5 years

• Safety and Tolerability of Olaparib Plus Bevacizumab

  Through study completion, an average of 1.5 years

• To evaluate the failure rate for the VHIOCARD-300 test and SOPHiA DD Dx HRD Solution.

  Through study completion, an average of 1.5 years

Study Arms (2)

HRD positive arm

EXPERIMENTAL

Patient with harboring HRD tumor, that will receive olaparib in combination with bevacizumab

Drug: Bevacizumab; Drug: Olaparib

HRD negative arm

OTHER

Control group receiving bevacizumab alone as standard of care.Patient with non harboring HRD tumor, that will receive bevacizumab

Drug: Bevacizumab

Interventions

Bevacizumab DRUG

Bevacizumab dosing is at 15 mg/kg every 3 weeks as an intravenous infusion.

HRD negative arm; HRD positive arm

Olaparib DRUG

Olaparib dosing is oral at 300 mg twice daily

HRD positive arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with newly diagnosed high- grade serous or endometrioid Ovarian cancer, primary peritoneal cancer and/or fallopian-tube cancer. I-3-3 At an advanced stage: FIGO stage IIIB, IIIC, or IV of the 1988 FIGO classification (see appendix 1).
• Patient who has completed prior to enrollment first line platinum-taxane chemotherapy:
• Platinum-taxane based regimen must have consisted of
• minimum of 6 treatment cycles and a maximum of 8. However, if platinum-based therapy must be discontinued early as a result of non-hematological toxicityspecificallyrelated to the platinum regimen, (i.e. neurotoxicity, hypersensitivity etc.), patient must have received a minimum of 4 cycles of the platinum regimen.
• Patient must have received prior to enrollment a minimum of 3 cycles of bevacizumab in combination with the 3 last cycles of platinum-based chemotherapy. Only in case of interval debulking surgery, it is allowed to realize only 2 cycles of bevacizumab in combination with the last 3 cycles of platinum-based chemotherapy.
• Patient must be prior to enrollment without evidence of disease (NED) or in complete response (CR) or partial response (PR) from the first line treatment. There should be no clinical evidence of disease progression (physical exam, imagery, CA 125) throughout he first line treatment and prior to study enrollment.
• Patient must be randomized at least 4 weeks and no more than 8 weeks after her last dose of chemotherapy (last dose is the day of the last infusion) and all major toxicities from theprevious chemotherapy must have resolved to CTCAE grade 1 or better (except alopecia and peripheral neuropathy).
• Patient must have normal organ and bone marrow function:
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (see appendix 3)
• Formalin fixed, paraffin embedded (FFPE) tumor sample from the primary cancer must be available for central BRCA testing and test result must be available for stratification.

You may not qualify if:

• Non-epithelial origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors).
• Ovarian tumors of low malignant potential (e.g. borderline tumors) or mucinous carcinoma.
• Other malignancy within the last 5 years except:
• Patient with myelodysplastic syndrome/acute myeloid leukemia history.
• Major surgery within 4 weeks of starting study treatment and patient must have recovered from any effects of any major surgery.
• Any previous treatment with PARP inhibitor, including olaparib.
• Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
• Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy.
• Clinically significant (e.g. active) cardiovascular disease, including:
• Myocardial infarction or unstable angina within ≤ 6 months of enrollment,
• New York Heart Association (NYHA) ≥ grade 2 congestive heart failure (CHF) (see appendix 5).
• Poorly controlled cardiac arrhythmia despite medication (patient with rate controlled atrial fibrillation are eligible), or any clinically significant abnormal finding on resting ECG,
• Peripheral vascular disease grade ≥ 3 (e.g. symptomatic and interfering with activities of daily living \[ADL\] requiring repair or revision)
• Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub-Arachnoids Hemorrhage (SAH) within 6 months prior to enrollment.
• History or evidence of hemorrhagic disorders within 6 months prior to enrollment.

Sponsors & Collaborators

• Vall d'Hebron Institute of Oncology: lead

Study Sites (1)

Vall d'Hebron Institute of Oncology

Barcelona, Spain

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Bevacizumab; olaparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ana Oaknin

  Vall d'Hebron Institute of Oncology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ana Oaknin

CONTACT

+34 934893000; aoaknin@vhio.net

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2024
• First Posted: April 22, 2024
• Study Start: February 6, 2024
• Primary Completion: March 1, 2024
• Study Completion: September 1, 2025
• Last Updated: May 9, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)